The objective of this Phase I project is to test and develop, using primate coronary artery vascular muscle cells in vitro, a novel estrogen receptor beta (ERbeta) selective (over ERalpha) agonist that is highly effective for protecting coronary arteries against hyperreactivity and also for relieving cardiovascular menopausal symptoms of ovarian steroid deficiency. Such cardiovascular hyperreactivity appears to result from the deficiency of balanced estrogen ERbeta versus ERalpha receptor stimulation after the cessation of ovarian function. This project will examine the effect of the ERbeta Agonist (ERbetaA), which is a natural human steroid metabolite, for the novel indication as a genomic repressor of reactivity in rhesus coronary vascular muscle cell experiments. This project is addressed to the challenge of reduction of coronary dysfunction, disability, and fatalities in menopausal women. Cardiovascular disease, the leading risk of death for women and men over age 50, mechanisms related to declining steroid production and steroid receptor balance are not well understood. The proposed ERbetaA formulation has been designed to significantly improve this situation and enhance quality of life in both women and men. The new commercial product will be a formulation designed to advance the present state by providing the first agent to offer ERbeta selective stimulation. The ERbetaA profile is salutary as it includes protection against coronary hyperreactivity while simultaneously lowering the risk of breast and uterine cancer. Furthermore, the need for only a low concentration of this bioidentical metabolite portends an excellent safety and side-effect prospect. Selective stimulation of ERbeta appears ideal because of this multifaceted protection against coronary hyperreactivity and of breast and uterine carcinomas.